Filgrastim is a hematological growth factor that can release neutrophils and autologous stem cells from the bone marrow of an individual. These can maximize in 4-5 days after daily subcutaneous injection (Grigg et al., Blood 1995, (86): 4437-4445) and create circulating stem and immune cells that can be harvested.
Examples in animal studies suggest reimplantation or reinfusion of stem cells in neurological conditions like acute stroke or trauma. These studies have been done with umbilical cord blood as well as donor stem cells from fetal animals or cultures. Some animal models of acute stroke have tried this with mixed results, and a brief human trial did not show significance that was seen in animal models, mainly in rats (Moriya et al., J. Stroke Cerebrovasc Dis. 2013 October; 22(7):1088-97). This animal work is reflected in U.S. Pat. No. 7,785,601 for animal models of Parkinson's disease.
WO2008/031448A1 discloses extraction and growing of stem cells with filgrastim preparation. U.S. Pat. No. 8,524,655 shows animal use for acute ischemia after 3-4 hours of injury. However, this does not reflect chronic long term damage perhaps weeks, months, or years later.
In a few human acute stroke studies there are limited data suggesting some mild trend to improve by using reinfused hematological peripheral stem cells, but changes in clinical imaging or length of hospital stay have not been found. Filgrastim has been used without harvesting in acute models of animal and human stroke patients. In controlled human studies designed for acute ischemic damage, 150-300 microgram per Kg of filgrastim did initially, in acute stroke, cause some improvement and was shown to have no major adverse effect from injection (Moriya et al, 2013; Shyu et al. 2006). However, in a larger controlled trial (128 microgram/Kg in acute stroke vs control in 328 patients), there were no objective changes seen between injection group and controls to really change post-stroke outcome (Ringelstein et al., 2013).
In chronic brain injury after head trauma, there is evidence that chronic inflammatory changes may persist, and cause long term progression and lack of regaining new neuronal connections and functional improvement. In acute concussion and post-concussion syndrome there may also be residual glial activation in the CNS that promotes chronic inflammation. Peripheral White Blood Cell Count (WBC) with neutrophils are especially able to modify or influence the state of inflammation in a given individual, as stem cells released may down regulate an overly-activated pro-inflammatory state. Glial CNS activation may be modified from peripheral immune factors, which peripheral hematological stem cells released by filgrastim may produce.
Applicant has written articles on and obtained patents directed to inflammatory cytokines, immune mechanism, and treatment options for pervasive development disorders, such as epilepsy, autism, and autism spectrum conditions. See, e.g., U.S. Pat. Nos. 7,456,224; 7,709,213; 8,354,438; and 8,741,847. The entireties of these U.S. patents are incorporated herein by reference. Further, Applicant has extensive research in conditions related to inflammation in form of cytokine and other pro-inflammatory agents (e.g., such as tumor necrosis factor TNF-α, TNF-β, interleukin IL-1a, IL-1b, IL-13, IL-6, and IL-10) as well as similar mechanisms involving neuronal CNS inflammation driven by chronic glial inflammatory response post-injury.